Instruments such as scanning electron microscopes, focused ion beam instruments, x-ray photoelectron spectrometers, and time-of-flight secondary ion mass spectrometers are often useful to researchers and technicians in the field of materials science and the semiconductor industries. In these instruments, wafers composed of silicon, gallium arsenide, indium phosphate, quartz, silica, germanium or sapphire (to name a few) are processed and/or analyzed for use as a substrate for electrical devices and thin films. These instruments are normally equipped with a stage for mounting a sample holder that holds the wafer or other flat substrate in place. Different sample holding mechanisms are known for use in these charged particle beam imaging and compositional analysis instruments due to the significant role they play in producing high quality data. Existing sample holders are limited in various ways, however. For example, instrument suppliers commonly provide a flat surface for gluing or taping the sample to the sample stage, but these methods are often unreliable and have other undesirable effects in precision instrumentation. The available mechanical clamping mechanisms tend to be large, challenging to use, and accommodate a small number of samples. Accordingly, there is a need for improved sample holders for such applications.